Motility enhancement by tumor-derived mutant E-cadherin is sensitive to treatment with epidermal growth factor receptor and phosphatidylinositol 3-kinase inhibitors

Margit Fuchs, Peter Hutzler, Ingrid Brunner, Jürgen Schlegel, Jörg Mages, Ute Reuning, Sandra Hapke, Justus Duyster, Setsuo Hirohashi, Takuya Genda, Michiie Sakamoto, Florian Überall, Heinz Höfler, Karl Friedrich Becker, Birgit Luber

研究成果: Article

19 引用 (Scopus)

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Diffuse-type gastric and lobular breast cancers are characterized by frequent mutations in the cell adhesion molecule E-cadherin. Here we report that tumor-associated mutations of E-cadherin enhanced random cell movement of transfected MDA-MB-435S mammary carcinoma cells as compared to wild-type (wt) E-cadherin-expressing cells. The mutations included in frame deletions of exons 8 or 9 and a point mutation in exon 8 which all affect putative calcium-binding sites within the linker region of the second and third extracellular domain. Motility enhancement by mutant E-cadherin was investigated by time-lapse laser scanning microscopy. Increased cell motility stimulated by mutant E-cadherin was influenced by cell-matrix interactions. The motility-increasing activity of mutant E-cadherin was blocked by application of pharmacological inhibitors of epidermal growth factor receptor and phosphatidylinositol (PI) 3-kinase. Investigation of the activation status of PI 3-kinase and the downstream signaling molecules Akt/protein kinase B and MAP kinase p44/42 showed that these kinases are not more strongly activated in mutant E-cadherin-expressing cells than in wt E-cadherin-expressing cells. Instead, the basal level of PI 3-kinase is necessary for mutant E-cadherin-enhanced cell motility. Our data suggest a critical role of E-cadherin mutations for the fine tuning of tumor cell motility.

元の言語English
ページ(範囲)129-141
ページ数13
ジャーナルExperimental Cell Research
276
発行部数2
DOI
出版物ステータスPublished - 2002 1 1
外部発表Yes

ASJC Scopus subject areas

  • Cell Biology

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    Fuchs, M., Hutzler, P., Brunner, I., Schlegel, J., Mages, J., Reuning, U., Hapke, S., Duyster, J., Hirohashi, S., Genda, T., Sakamoto, M., Überall, F., Höfler, H., Becker, K. F., & Luber, B. (2002). Motility enhancement by tumor-derived mutant E-cadherin is sensitive to treatment with epidermal growth factor receptor and phosphatidylinositol 3-kinase inhibitors. Experimental Cell Research, 276(2), 129-141. https://doi.org/10.1006/excr.2002.5518